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八角莲诱导 AGS 胃腺癌细胞凋亡和 G1 期细胞周期阻滞。

Induction of apoptosis and G1 phase cell cycle arrest by Aster incisus in AGS gastric adenocarcinoma cells.

机构信息

Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 45813, Republic of Korea.

Institute of Marine Biotechnology, College of Natural Sciences, Pukyong National University, Busan 45813, Republic of Korea.

出版信息

Int J Oncol. 2018 Nov;53(5):2300-2308. doi: 10.3892/ijo.2018.4547. Epub 2018 Aug 30.

Abstract

In recent decades, various bioactive compounds from plants have been investigated for their potential use in the treatment of diseases in humans. Aster incisus extract (AIE) is the extract of a common plant that is mostly found in Asia. It has traditionally been used for medicinal purposes in South Korea. In this study, we evaluated the potential anticancer effects of a methanolic extract of Aster incisus in a normal human cell line (HaCaT keratinocytes) and in 4 different types of human cancer cell lines (A549, lung cancer; Hep3B, liver cancer; MDA‑MB‑231, breast cancer; and AGS, gastric cancer). The HaCaT, A549, Hep3B, MDA‑MB‑231 and AGS cells were treated with various concentrations of AIE and following treatment, cell survival was evaluated. Additional analyses, such as WST-1 assay, western blot analysis, DAPI staining, flow cytometry, immunofluorescence staining and wound healing assay were performed to elucidate the mechanisms and pathways involved in the cell death induced by AIE. Treatment with AIE induced morphological changes and considerably reduced the viability of the both normal and cancer cell lines. Further analysis of the AGS gastric cancer cells revealed that AIE led to the induction of apoptosis and a high accumulation of cells in the G1 cell phase following treatment with AIE in a dose-dependent manner. The results also revealed that AIE successfully suppressed the migration of the AIE-treated AGS cells. The results of western blot analysis indicated that AIE increased the expression of pro-apoptotic proteins, particularly Bid, Bad, Bak, cytochrome c, apoptosis inducing factor (AIF), cleaved caspase‑3, -8 and -9 and cleaved poly(ADP-ribose) polymerase (PARP). Additionally, AIE decreased the expression of the anti-apoptotic proteins, Bcl-2 and Bcl-xL. On the whole, the findings of this study demonstrate that AIE induces apoptosis through the activation of the caspase‑dependent pathway mediated by the mitochondrial pathway and by arresting the cell cycle in AGS cells.

摘要

近几十年来,人们一直在研究各种植物中的生物活性化合物,以寻找其在人类疾病治疗中的潜在用途。苍耳提取物(AIE)是一种常见植物的提取物,主要分布在亚洲。在韩国,它传统上被用于药用目的。在这项研究中,我们评估了苍耳甲醇提取物在正常人角质形成细胞系(HaCaT 角质形成细胞)和 4 种不同类型的人类癌细胞系(A549、肺癌;Hep3B、肝癌;MDA-MB-231、乳腺癌;和 AGS、胃癌)中的潜在抗癌作用。用不同浓度的 AIE 处理 HaCaT、A549、Hep3B、MDA-MB-231 和 AGS 细胞,然后评估细胞存活率。还进行了 WST-1 测定、western blot 分析、DAPI 染色、流式细胞术、免疫荧光染色和划痕愈合试验等额外分析,以阐明 AIE 诱导细胞死亡所涉及的机制和途径。AIE 处理导致形态变化,并显著降低正常和癌细胞系的活力。对 AGS 胃癌细胞的进一步分析表明,AIE 以剂量依赖性方式诱导细胞凋亡,并使细胞大量积累在 G1 期。结果还表明,AIE 成功抑制了 AIE 处理的 AGS 细胞的迁移。western blot 分析结果表明,AIE 增加了促凋亡蛋白的表达,特别是 Bid、Bad、Bak、细胞色素 c、凋亡诱导因子(AIF)、cleaved caspase-3、-8 和 -9 以及 cleaved 多聚(ADP-核糖)聚合酶(PARP)。此外,AIE 降低了抗凋亡蛋白 Bcl-2 和 Bcl-xL 的表达。总的来说,这项研究的结果表明,AIE 通过激活 caspase 依赖性途径诱导 AGS 细胞中的细胞凋亡,该途径通过线粒体途径介导,并通过阻止细胞周期在 AGS 细胞中进行。

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